The Molecular and Cellular Oncogenesis Program (MCO) is comprised of eleven investigators who work collaboratively in broad areas of cancer biology. Over the last budget period, the MCO Program has undergone an extensive realignment in research focus, thematic areas of collaboration and Program membership. In line with the strategic reorganization ofthe Cancer Center, the MCO Program appointed a new Program Leader (Dr. Murphy), recruited four new investigators at all academic ranks, and received one faculty member (Dr. Janicki) from the Gene Expression and Regulation (GER) Program. Concomitantly, three MCO members transferred to the newly created Program in Tumor Microenvironment and Metastasis (TMM). As a result, the MCO Program is now a more focused and highly collaborative research initiative, bringing together multidisciplinary expertise around three general flagship themes: Mechanisms of growth control (i); Cancer biomarkers and bio-signatures (ii); and Targeted cancer therapeutics (iii). The overarching goal of the Program is to combine a mechanistic understanding of cancer signaling networks with novel molecular approaches to disease diagnosis and treatment, along the continuum of basic, translational and patient-oriented cancer research. Synergy among the scientists is facilitated by a strong programmatic foundation in computational and integrative biology, a broad utilization of Cancer Center Shared Resources, and productive inter-programmatic and inter-institutional collaborations. Over the last budget period, MCO investigators made impressive gains on a broad portfolio of scientific discoveries in line with Program goals. The National Cancer Institute (NCI) funding base of the Program has grown by 27% compared to the last budget period, from $2.05 million in 2008 to $2.79 million in 2013 (direct costs), and the rate of collaborative publications has increased by more than five-fold, from 6.9% in 2008 to 36% in 2013 (total of intra- and inter-programmatic publications), with a total of 187 peer-reviewed cancer-relevant publications. MCO investigators continue to lead large programmatic and disease-relevant collaborations (Program Project grants, SPORE), contribute substantially to the translational mission of the Cancer Center in the Melanoma and Ovarian Cancer Research Continuum Signatures, and actively participate in education, mentoring and career development of faculty and trainees. The MCO Program will continue to build on these strengths during the next budget period, further expanding its unifying role as a multidisciplinary hub for basic and translational cancer research.